Marine Drug Discovery: Anti-obesity Mechanism of Palmaria Mollis in Zebrafish and Mice

Abstract

Background: The red seaweed Palmaria mollis (PM) has recently become popular as foodstuffs due to their relatively high proteins, in addition to their potential as a source of biofunctional molecules and antioxidant ingredients. We previously performed small-scale screening with diet-induced obese (DIO) zebrafish, and found that PM is one of strong candidates for the treatment of obesity and its-related diseases.

Methods: We fed PM-containing feed to DIO-zebrafish and mice and evaluated the effects on obese phenotypes, including body weight gain, dyslipidaemia, hepatic steatosis and visceral adiposity. To clarify the anti-obesity mechanisms of PM, we performed gene expression analyses of the liver and visceral adipose tissues in these model animals.

Results: PM suppressed hepatic steatosis, dyslipidaemia and visceral adiposity both in DIO-zebrafish and mice, especially in the early stage of obese development. In liver tissues of DIO-zebrafish and mice, PM upregulated peroxisome proliferator-activated receptor alpha (PPARA) pathways and downregulated PPARG pathways, suggesting that the lipid-lowering effect of PM might be caused by activation of beta-oxidation and inhibition of lipogenesis. In visceral adipose tissues, while PM showed the similar effects in zebrafish and mice, their gene expression changes were different between these DIO-animals. PM downregulated genes involved in early and late adipocyte differentiation in zebrafish, but not in mice. Instead, PM suppressed the elevation of sterol regulatory element binding transcription factor 1 in obese mice.

Conclusion: We demonstrated that PM has a powerful lipid-lowering effect and prevention of hepatic steatosis and visceral adiposity for the first time. Intake of PM as a functional food may be suitable for obesity prevention and reduction of the prevalence of obesity-related diseases. Phenotype-driven zebrafish screening would facilitate the drug discovery from marine bioresources. We further continue zebrafish screening to find the bioactive compounds in PM.